ArticleRoyal Society open science2023
Molecular interaction of a putative inhibitor with bacterial SHV, an enzyme associated with antibiotic resistance.
Article in Royal Society open science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A phenotypic drug discovery approach by latent interaction in deep learning.Royal Society open science · 2024Article
- Molecular interaction of a putative inhibitor with bacterial SHV, an enzyme associated with antibiotic resistance.Royal Society open science · 2023Article
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Authors and funding
3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Tackling the ever-looming threat of antibiotic resistance remains a challenge for clinicians and microbiologists across the globe. Sulfhydryl variable (SHV) is a known bacterial enzyme associated with antibiotic resistance. The SHV enzyme has many variants. The present article describes identification and molecular interaction of a putative inhibitor with the bacterial SHV enzyme as a step towards novel antibacterial drug discovery. The MCULE-platform was used for screening a collection of 5 000 000 ligand molecules to evaluate their binding potential to the bacterial SHV-1 enzyme. Estimation of pharmacokinetic features was realized with the aid of the 'SWISS ADME' tool. Toxicity-checks were also performed. The docked complex of 'the top screened out ligand' and 'the bacterial SHV-1 protein' was subjected to molecular dynamics simulation of 101 ns. The obtained ligand molecule, 1,1'-(4H,8H-Bis[1,2,5]oxadiazolo[3,4-b:3',4'-e]pyrazine-4,8-diyl)diethanone, displayed the most favourable binding interactions with bacterial SHV-1. A total of 15 amino acid residues were found to hold the ligand in the binding site of SHV-1. Noticeably, 12 of the 15 residues were found as common to the binding residues of the reference (PDB ID: 4ZAM). The RMSD values plotted against the simulation time showed that nearby 11 ns, equilibrium was reached and, thenceforth, the 'SHV-1-Top ligand' complex remained typically stable. Starting from around 11 ns and straight to 101 ns, the backbone RMSD fluctuations were found to be confined inside a range of 1.0-1.6 Å. The ligand, 1,1'-(4H,8H-Bis[1,2,5]oxadiazolo[3,4-b:3',4'-e]pyrazine-4,8-diyl)diethanone, satisfied ADMET criteria. Furthermore, the practicability of the described 'SHV-1-Top ligand' complex was reinforced by a comprehensive molecular dynamics simulation of 101 ns. This ligand hence can be considered a promising lead for antibiotic design against SHV-1 producing resistant bacteria, and thus warrants wet laboratory evaluation.
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